Effectiveness of nirmatrelvir-ritonavir on severe outcomes of COVID-19 in the era of vaccination and Omicron: An updated meta-analysis.

Nirmatrelvir-ritonavir (NR) was approved to treat SARS-CoV-2 positive outpatients at high risk of progression to severe disease, based on a randomized trial in unvaccinated patients. Effectiveness in vaccinated patients and against Omicron has not yet been confirmed by clinical trial data, but a recent meta-analysis suggested good real-world effectiveness based on 12 studies. We updated this meta-analysis by searching Medline and Embase databases for studies assessing effectiveness of NR on mortality, hospitalization, composite outcome of hospitalization and/or death, and progression to severe disease, published between October 1, 2022 and May 22, 2023. Random effects meta-analysis and subgroup analysis for vaccinated patients was performed. A total of 32 studies were included in the meta-analysis. Pooled RR for the effect of NR on mortality, hospitalization, hospitalization and/or mortality, and progression to severe disease were 0.36 (95% confidence interval [CI]: 0.25-0.52), 0.43 (CI: 0.37-0.51), 0.52 (CI: 0.45-0.61) and 0.54 (CI: 0.41-0.73), respectively. A subgroup analysis on vaccinated patients indicated lower effectiveness of NR on mortality (RR: 0.55, CI: 0.45-0.68), but similar effectiveness for hospitalization, hospitalization and/or mortality, or progression to severe disease (RR: 0.52, 0.58, and 0.66, respectively). This updated meta-analysis robustly confirms the protective effects of NR on severe COVID-19 outcomes.

Cervical cancer screening and outcomes for women under 25 years of age in Belgium: a 10-year nationwide study.

OBJECTIVE: The aim of the study was to describe trends in cervical cancer screening and outcomes for women under 25 years of age in Belgium between 2010 and 2019 in response to a changed reimbursement policy. MATERIALS AND METHODS: We used the databases of the National Health Insurance Institute (RIZIV/INAMI) and the Belgian Cancer Registry (BCR) for a nationwide description of cervical screening, subsequent diagnostic procedures and outcomes for women younger than 20 years and women aged 20-25 years between 2010 and 2019. RESULTS: Over a 10-year period, the number of cytology screening tests and annual screening rates in women younger than 25 years have been reduced by 50%, but no increases in invasive cervical cancer or high-grade intraepithelial lesion diagnoses were observed. The major determinant of this decreased overscreening has been the limitation of reimbursement in 2013 to once every 3 years instead of once every 2 years. In women aged 25-29 years, there is no increase in invasive cervical cancer diagnoses after decreased screening of women younger than 25 years. To detect 29 invasive cervical cancers in women younger than 25 during the 10-year study period, a total of 5606 conizations were performed and 43 million EUR of Belgian health insurance budget was spent. Since the cost of hospitalization, sickness leave and negative psychological impact were not included in our estimation, these costs are underestimated. CONCLUSION: Incidence of cervical cancer in women under 25 years remains low and screening is not effective in preventing cervical cancer, although there is clear evidence of potential reproductive harm and financial cost. We state that restricting reimbursement of cervical cancer screening before the age of 25 will improve guideline adherence and decrease healthcare expenditures without negatively impacting the health of the population.

Ovarian Clear Cell Carcinoma with Functioning Stroma and Associated Endometrial Intraepithelial Neoplasia.

We report the case of a 79-year-old woman with a large pelvic mass and postmenopausal bleeding, associated with hyperestrogenism. A pelvic MRI shows the presence of a large mass of 12.6 cm originating from the right ovary without signs of metastasis. A total abdominal hysterectomy with unilateral salpingooophorectomy was performed, knowing the patient underwent a left salpingooophorectomy decades ago. The pathological findings showed an ovarian clear cell carcinoma (pT1A) with associated endometrial intraepithelial neoplasia. There is convincing evidence that the production of estrogen is located in the activated ovarian stroma. This supports the view that functioning stroma of ovarian cancer can lead to hyperestrogenism and eventually endometrial cancer.

Characterisation of the human uterine microbiome in non-pregnant women through deep sequencing of the V1-2 region of the 16S rRNA gene.

Background. It is widely assumed that the uterine cavity in non-pregnant women is physiologically sterile, also as a premise to the long-held view that human infants develop in a sterile uterine environment, though likely reflecting under-appraisal of the extent of the human bacterial metacommunity. In an exploratory study, we aimed to investigate the putative presence of a uterine microbiome in a selected series of non-pregnant women through deep sequencing of the V1-2 hypervariable region of the 16S ribosomal RNA (rRNA) gene. Methods. Nineteen women with various reproductive conditions, including subfertility, scheduled for hysteroscopy and not showing uterine anomalies were recruited. Subjects were highly diverse with regard to demographic and medical history and included nulliparous and parous women. Endometrial tissue and mucus harvesting was performed by use of a transcervical device designed to obtain endometrial biopsy, while avoiding cervicovaginal contamination. Bacteria were targeted by use of a barcoded Illumina MiSeq paired-end sequencing method targeting the 16S rRNA gene V1-2 region, yielding an average of 41,194 reads per sample after quality filtering. Taxonomic annotation was pursued by comparison with sequences available through the Ribosomal Database Project and the NCBI database. Results. Out of 183 unique 16S rRNA gene amplicon sequences, 15 phylotypes were present in all samples. In some 90% of the women included, community architecture was fairly similar inasmuch B. xylanisolvens, B. thetaiotaomicron, B. fragilis and an undetermined Pelomonas taxon constituted over one third of the endometrial bacterial community. On the singular phylotype level, six women showed predominance of L. crispatus or L. iners in the presence of the Bacteroides core. Two endometrial communities were highly dissimilar, largely lacking the Bacteroides core, one dominated by L. crispatus and another consisting of a highly diverse community, including Prevotella spp., Atopobium vaginae, and Mobiluncus curtisii. Discussion. Our findings are, albeit not necessarily generalizable, consistent with the presence of a unique microbiota dominated by Bacteroides residing on the endometrium of the human non-pregnant uterus. The transcervical sampling approach may be influenced to an unknown extent by endocervical microbiota, which remain uncharacterised, and therefore warrants further validation. Nonetheless, consistent with our understanding of the human microbiome, the uterine microbiota are likely to have a previously unrecognized role in uterine physiology and human reproduction. Further study is therefore warranted to document community ecology and dynamics of the uterine microbiota, as well as the role of the uterine microbiome in health and disease.